Potential of hydrogen control process applied to preparation of isiomerazole

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a pH value control process applied to preparation of isimerazole. A verification result shows that the product is reasonable in process, high in operability, good in compatibility with existing equipment in a workshop, capable of being smoothly produced on the existing equipment in the workshop, good in reproducibility, free of any deviation in the production process, and capable of being widely applied to industrial production, and various data in the verification process are within the range of process requirements and verification scheme requirements. Therefore, the production process of the product can meet the requirements. Quality research results show that various indexes of a pilot-scale test product are ideal, and compared with an original research product, the indexes are not obviously different, and the quality is equivalent.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a pH control process used in the preparation of esomeprazole. Background Art

[0002] Esomeprazole is the S-isomer of omeprazole. It reduces gastric acid secretion through specific proton pump inhibition. The R-isomer and S-isomer of omeprazole have similar pharmacodynamic properties. Esomeprazole is a weakly alkaline drug. It is concentrated and converted into an active form in the high acid environment of the acid secretory microtubules of parietal cells, thereby inhibiting the H+ / K+-ATPase (proton pump) in this area, and inhibiting both basal gastric acid secretion and gastric acid secretion after stimulation.

[0003] Freeze-drying technology refers to a technology that directly sublimates water from solid to gas in a vacuum environment below zero degrees, extracting the moisture in the product and thus completely preserving the activity of biological components.

[0004] Esomeprazole is a lyophilized powder for injection. The production process mainly includes drug solution preparation, sterilization filtration, and freeze drying. The key steps include the pH range of the drug solution, the temperature and light stability of the drug solution, filtration, freeze drying, etc.

[0005] Visible foreign matter often exists in the research and development and production process of injections, eye drops and other liquid medicines. It is an insoluble substance that can be observed visually under specific conditions. Its particle size or length is usually greater than 50μm. The light inspection method is usually used to detect visible foreign matter.

[0006] The so-called insoluble particles in injections refer to tiny granular impurities that are contaminated by drugs through various channels during production or application. Their particle size ranges from 1 micron to 50 microns. They are invisible to the naked eye, mobile, non-metabolic harmful particles. Summary of the invention

[0007] The object of the present invention is to provide a pH control process for the preparation of esomeprazole, which is conducive to large-scale mass production and optimizes the freeze-drying process of the preparation.

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] A pH control process for preparing esomeprazole comprises the following steps:

[0010] Through screening experiments and pH value screening experiments, the pH value of the esomeprazole intermediate solution was set between 11.0-11.5, and the pH value of the finished product was between 10.0-11.0.

[0011] Also included are steps for recovering chloroform, ethyl acetate and acetonitrile:

[0012] Wash chloroform or ethyl acetate with water until neutral, separate the water layer, and then distill under normal pressure. When recovering chloroform, collect the 60-62°C fraction for use, when recovering ethyl acetate, collect the 76-78°C fraction for use, and when recovering acetonitrile, collect the 81-83°C fraction for use.

[0013] It also includes the steps of recovering methanol, ethanol and isopropanol:

[0014] In the distillation tower, when recovering methanol, collect the 64-65℃ fraction and use it, when recovering ethanol, collect the 78-79℃ fraction and use it, when recovering isopropanol, collect the 81-83℃ fraction and use it.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The verification results show that the product has a reasonable process, strong operability, good compatibility with existing equipment in the workshop, can be successfully produced on the existing equipment in the workshop, has good reproducibility, and all data in the verification process are within the process requirements and verification plan requirements. There is no deviation in the production process, which proves that the production process of this product can meet the requirements. The quality research results show that the indicators of the pilot product of this product are relatively ideal. Compared with the original product Nexin Powder Injection, there is no significant difference in various indicators, and the quality is equivalent. DETAILED DESCRIPTION

[0017] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0018] Example

[0019] A pH control process for preparing esomeprazole comprises the following steps:

[0020] Through screening experiments and pH value screening experiments, the pH value of the esomeprazole intermediate solution was set between 11.0-11.5, and the pH value of the finished product was between 10.0-11.0.

[0021] Also included are steps for recovering chloroform, ethyl acetate and acetonitrile:

[0022] Wash chloroform or ethyl acetate with water until neutral, separate the water layer, and then distill under normal pressure. When recovering chloroform, collect the 60-62°C fraction for use, when recovering ethyl acetate, collect the 76-78°C fraction for use, and when recovering acetonitrile, collect the 81-83°C fraction for use.

[0023] It also includes the steps of recovering methanol, ethanol and isopropanol:

[0024] In the distillation tower, when recovering methanol, collect the 64-65℃ fraction and use it, when recovering ethanol, collect the 78-79℃ fraction and use it, when recovering isopropanol, collect the 81-83℃ fraction and use it.

[0025] This product is for injection, so the pH value was studied and included in the quality standard. The initial measurement results of each batch of samples were between 10.0 and 11.0. According to the results of the sample batch inspection and stability study (no change in the stability study), the pH value measurement range of this product is specified to be 10.0 to 11.0.

[0026] The pH value test results of the stability samples of this product are shown in Table 1 below:

[0027] Table 1. pH checklist for stability samples

[0028]

[0029] The production process of this product is conventional, stable and controllable, with good reproducibility, and can meet GMP specifications and large-scale production requirements. Through methodological research and verification, a practical drug quality standard has been established to effectively control the quality of this product.

Claims

1. A pH control process for the preparation of esomeprazole, characterized in that The steps include: Through screening experiments and pH value screening experiments, the pH value of the esomeprazole intermediate solution was set between 11.0-11.5, and the pH value of the finished product was between 10.0-11.

0.

2. The pH control process for preparing esomeprazole according to claim 1, characterized in that Also included are steps for recovering chloroform, ethyl acetate and acetonitrile: Wash chloroform or ethyl acetate with water until neutral, separate the water layer, and then distill under normal pressure. When recovering chloroform, collect the 60-62°C fraction for use, when recovering ethyl acetate, collect the 76-78°C fraction for use, and when recovering acetonitrile, collect the 81-83°C fraction for use.

3. The pH control process for preparing esomeprazole according to claim 1, characterized in that It also includes the steps of recovering methanol, ethanol and isopropanol: In the distillation tower, when recovering methanol, collect the 64-65℃ fraction and use it, when recovering ethanol, collect the 78-79℃ fraction and use it, when recovering isopropanol, collect the 81-83℃ fraction and use it.

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